TREATMENT WITH CYTOMEGALOVIRUS (CMV) PP65-SPECIFIC LYPHOCYTES IN PATIENTS WITH CMV REACTIVATION OR CMV DISEASE AFTER ALLOGENEIC STEM CELL TRANSPLANTATION.

This is an open-label non-randomized phase I/II feasibility study to treat patients with persistent CMV reactivation or CMV disease after alloSCT with administration of CMV pp65-specific T cells generated by use of a CMV pp65 protein-spanning peptide pool.

Patients after alloSCT with a CMV seropositive donor will be monitored weekly for CMV reactivation using PCR for the detection of CMV DNA. In case of CMV reactivation (defined as CMV DNA load >1000 cp/ml) patients will be treated with antiviral therapy according to standard protocols.

For patients with CMV reactivation who fail antiviral therapy (defined as CMV reactivation treatment failure: persistent CMV DNA load of more than 1000 cp/ml or CMV disease after 2 weeks of adequate treatment with antiviral therapy or relapse of CMV DNA load of more than 1000
cp/ml within 4 weeks after adequate treatment with antiviral therapy or contraindication for treatment with antiviral therapy at the discretion of the physician) or develop CMV disease (organ dysfunction (pneumonitis, enteritis, retinitis, encephalitis, hepatitis, and bone marrow suppression) due to CMV infection), CMV pp65-specific CD4+ and CD8+ T cells will be generated from donor PBMC by overnight in vitro stimulation with CMV pp65 peptide pools. CMV-specific CD4+ and CD8+ T cells will be isolated based on their IFNg production and administered to the patient directly after quality control. If alloSCT was performed using CD34 positive cell selection and the CD34 negative subfraction has been cryopreserved at a GMP facility, this fraction can also be used for selection of CMV-specific T cells. Antiviral therapy will be continued after infusion of CMV pp65-specific T cells according to standard antiviral treatment protocols at the discretion of the physician.
In case of ongoing CMV reactivation or CMV disease the infusion of CMV pp65-specific T cells may be repeated 2 times with at least 4 weeks interval. The patient will be monitored for adverse events and for effect on CMV DNA load. Follow-up of patients will be performed until 6 months after infusion of CMV pp65-specific T cells or until subsequent DLI, whichever comes first.

N/A

1. Weekly, first 3 months after infusion;

2. Monthly, 3-6 moths after infusion.

Infusion of CMV pp65-specific T-cells.